Zika Virus, the Story So Far

Hugh Pennington

An Aedes aegypti mosquito stops for lunch

On 18 April 1947 in a cage on a tree platform in the Zika Forest in Uganda, rhesus monkey number 766 developed a fever. Its serum was inoculated into the brains of mice. They fell ill. Zika virus had been discovered. The sentinel monkey researchers were the virologist George Dick and the entomologist Alexander Haddow, based at the Rockefeller Foundation Yellow Fever Laboratories in Entebbe. Haddow went on to build a 120-foot steel tower in the forest to study high-flying mosquitoes and their viruses. The best time and place to find Zika virus was in the evening, 80 to 100 feet above the forest floor.

The first human case to be described was in 1964 in another Entebbe virologist, David Simpson; he had a 36-hour fever, some back pain, a headache and a rash. He was better by day three. Antibody studies in Nigeria in the early 1970s found that 40 per cent of people had been infected at some time in the past.

For many years Zika virus resided quietly in the textbooks as a member of the Flavivirus family, a distant and unimportant relative of yellow fever, dengue and West Nile viruses. The books said that it caused only mild symptoms (or none at all), that it was spread by the bite of Aedes mosquitoes, that monkeys were an animal reservoir, and that it occurred in Africa, India and South East Asia.

An alarm bell rang in 2007 when an outbreak occurred on Yap Island in the southwestern Pacific. The infection was mild, with a rash, conjunctivitis and joint pains. But not only was the outbreak the biggest so far recorded – it was estimated that well over half the residents had been infected – the virus had travelled a long way to get to Yap. Perhaps it could spread to the Americas.

The bell rang again in late 2013 when a large outbreak started in French Polynesia, with the first report of the Guillain-Barré syndrome associated with a number of cases. Guillain-Barré is a neurological illness with paralysis as its main feature.

In May 2015 the first confirmed indigenous cases of Zika virus infection were reported in north-east Brazil. Since then it has spread across the country, and reached Mexico, Haiti, Puerto Rico, Barbados, Paraguay and other South American countries, though not Bolivia, Peru, Chile, Uruguay or Argentina.

But it is the reports of an increase in the number of children born in Brazil in 2015 with abnormally small heads – microcephaly – that have driven Zika to the top of the news. Microcephaly has many causes and is not new. Individuals with it appear on bas-reliefs on Aztec temples. So far, the link between its increase and Zika infections is only coincidence. Evidence demonstrating a definitive link in individual cases will be hard to get. Establishing whether a mother was infected during pregnancy will usually rely on antibody tests; the virus itself does not persist in the body after an acute infection. The close relationship between dengue virus and Zika makes it virtually impossible to know which virus could have stimulated an immune response. And dengue is currently on the rampage in Brazil. In 2015 there were 1.6 million suspected cases and 839 deaths. The failure of mosquito control is the main reason.

The eradication of Aedes aegypti (the mosquito that transmits both dengue and Zika) in Brazil was driven by the fear of another flavivirus it transmitted, yellow fever. A DDT programme started in 1947. Brazil was declared free of the mosquito in 1958. But in 1976 it came back, probably flying in from Venezuela and the Carribean. Dengue came into the country in 1981. The aim of eradicating Aedes aegypti was dropped and replaced with a control policy in 1986. The mosquito has thrived. It likes people and loves to lay its desiccation-resistant eggs in manmade water containers.

So the relentless spread of dengue after 1981 and Zika in 2015 is no surprise. The possible link between a Zika virus infection and microcephaly is surprising, however. Diseases caused by the other flaviviruses have been intensively studied for many years without microcephaly turning up as a complication. It hasn’t been clearly evident in Zika virus outbreaks elsewhere in the world. But flaviviruses mutate in real time. The classic example is West Nile virus. Isolated at the Rockefeller Yellow Fever labs in Uganda in 1937, like Zika it remained quiet for years. Then in the mid-1990s it got nastier, causing severe brain disease with epidemics in North Africa and Southern Europe. It took off in New York in 1999, and spread rapidly across the continent.

The genomes of the different Zika virus lineages are being sequenced. But developing a vaccine and ensuring that it is safe will take years. The quickest way to stop it in Brazil will be to attack the mosquitoes. The Olympics are near. Perhaps DDT will make a comeback.


  • 3 February 2016 at 6:03pm
    robertrickman says:
    DDT is not required. Oxford based company has a aedes mosquito control technology which has been extensively and successfully trialled in Brazil in the last few years to counter dengue. Their web site provides a detailed resource for some further understanding.

    • 4 February 2016 at 1:30pm
      Clive Ray says: @ robertrickman
      There is another interesting company involved in this, the website of which,, lists a Robert Rickman amongst its team members and includes Oxitex in its investment portfolio.

  • 3 February 2016 at 9:14pm
    brogers999 says:
    Stories are now appearing on internet that Oxitec's experiments in Brazil to control dengue are somehow connected to the outbreak of microcephaly, a condition not previously (to my knowledge) associated with Zika (or Dengue). The same mosquito species is involved, but I am not aware of any mechanistic theory for the connections being claimed. Is there any evidence for the claim that 'GMO mosquitoes' are implicated in this?

  • 3 February 2016 at 9:45pm
    Clive Ray says:
    According to the Ecologist, Oxitec's genetically modified mosquito trial was conducted in the very same area of Brazil that has seen the spike in cases of Zika Virus apparently associated with microcephaly. This may be mere coincidence, or it perhaps could be that Oxitec's trials present the cause of, rather than a solution to, the Zika problem. If this proves to be the case, perhaps DDT will be making a comeback.

    • 5 February 2016 at 1:51am
      brogers999 says: @ Clive Ray
      As you say, a coincidence, association not by any stretch causation, but the kind of coincidence that should pique further research to either confirm or disconfirm any connection. Rubella can cause fetal damage, but the Zika-microcephaly association, if confirmed, would be an extreme viral impact: smaller head & damaged brain.

  • 4 February 2016 at 9:21am
    blue_tree says:
    The previous occurrences of this virus did not produce microcephaly or affect people in the way that it is currently doing. The 'Africa monkey' always coincidentally discovered by a western scientist, that trope is exceedingly overwrought (unless said monkey was infected in the lab and then released into the wild). What happened between the date of alleged 'discovery' of virus, and its current manifestation in 2015? How did lie latent for so many years to re-emerge in a South American wilderness to such drastic outcome? What kind of virus has ever 'known' to target the embryo in a mother's womb? Microcephaly is not a widespread condition in the site of the virus' alleged discovery. Viruses mutate, yes, but to this extent? Something is missing in this story.

    • 4 February 2016 at 11:44am
      casualreader says: @ blue_tree
      Blue-tree asks, 'what kind of virus has ever 'known' to target the embryo in a mother's womb?' The Rubella virus has long been known to affect the foetus if contracted by a pregnant woman, sometimes resulting in miscarriage. If carried to term the infant's sight and hearing may be affected.

  • 4 February 2016 at 2:03pm
    John Cowan says:
    Despite the attempts of certain of my fellow countrymen to make political and economic capital of it ("Rachel Carson was a mass murderer!"), using DDT for the control of insect-born diseases has never been banned, only its indiscriminate use in agriculture. Indeed, it is precisely that use that has made DDT almost useless for disease control, as resistance to it is now extremely widespread among mosquitoes.

  • 5 February 2016 at 2:10pm
    brogers999 says:
    Rather than speculate further, I would urge reading of the Special Report on Zika virus in this week's Lancet. It conflates neurological disorders and microcephaly when it states that there was a "similar cluster in French Polynesia in 2014". It is not clear if there was microcephaly in French Polynesia, but also not clear yet whether there is an epidemic of microcephaly associated with Zika in Brazil due to reporting issues. I conclude that it is too early to jump to any conclusions. Not that it's a good idea to ever 'jump' to conclusions.

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